IGE-INDEPENDENT INTERLEUKIN-4 EXPRESSION AND INDUCTION OF A LATE-PHASE OF LEUKOTRIENE C4 FORMATION IN HUMAN BLOOD BASOPHILS

T-helper cells can differentiate into at least two subtypes secreting distinct profiles of cytokines, Th1 and Th2, regulating immunoprotection and different immunopathologies. Interleukin-4 (IL-4) is both the product and the inducer of Th2 cells, raising the question whether IL-4 can be produced in response to antigen-independent stimuli. Here we show that human basophils produce IL-4 on stimulation with IL-3 and C5a or C5a(desarg) in similar amounts as induced by IgE-receptor-cross-linking. C5a-induced IL-4 production requires the presence of IL-3, with little effect of the sequence of stimuli addition. No ''Th1-cytokines'' (interferon-gamma and IL-2) and even no ''Th2-cytokines'' (IL-3, IL-5, IL-10, and granulocyte-macrophage colony-stimulating factor) are produced by basophils in response to either IgE-dependent or IgE-independent activation, The generation of leukotriene C-4 (LTC(4)) is regulated in a similar manner. However, C5a induces a rapid, transient burst of leukotriene formation only if added after IL-3. Interestingly, upon prolonged culture, a late phase of continuous LTC, production is observed, which also requires two signals (IL-3 and C5a), but rather depends on their continuous presence than on their sequence of action. These data describe an antigen-independent pathway of very restricted IL-4 expression. Thus, basophils must be considered as central immunoregulatory cells of the innate immune system. Furthermore, the results show that LTC, can also be generated more continuously for many hours, a phenomenon that may be of particular importance in chronic allergic inflammation, such as asthma. (C) 1995 by The American Society of Hematology.